This is an R21 application to explore the development of an animal model to study the effects of parental and peripuberal exposure to nicotine. Nicotine remains an important drug of abuse worldwide. In the United States (U.S.), tobacco use is the single leading preventable cause of death. However, despite considerable negative publicity and health warnings, approximately 25 percent of the U.S. population still smoke. Aside from producing profound behavioral effects in the adult organism, nicotine also disrupts developmental processes in many species. Recent epidemiologic data suggest that fetal exposure to nicotine increases the risk for tobacco use during adolescence and adulthood, particularly in females. In addition, 75 percent of adult tobacco users report their first tobacco use occurred when they were "youngsters" (childhood or adolescence). In order to study this issue further, as well as to develop an animal model to elucidate potential underlying mechanisms, the effects of nicotine exposure during gestation on nicotine self-administration in adult male and female rat offspring will be studied. In addition, the effects of nicotine exposure during the periadolescent period on nicotine self-administration in adult offspring will be ascertained. It is hypothesized that nicotine exposure in utero will increase nicotine self-administration in adult offspring. Similarly, peripuberal exposure to nicotine also will increase nicotine self-administration during adulthood. The proposed studies will characterize the relationships between exposure to nicotine during critical periods of development and the acquisition, maintenance, extinction and re-initiation phases of nicotine self-administration. The results of these experiments should provide new and important insights on the relationships between prior nicotine exposure and nicotine-seeking behavior. In addition, since nicotine is considered as a "gateway" drug for the subsequent use of alcohol and other illicit drugs, the results of the proposed studies will lay the groundwork to further understand the factors which might increase vulnerability to drug addictions in general, and to nicotine abuse, in particular.